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Gene Expression Profiling Shows Medullary Breast Cancer Is a Subgroup of Basal Breast Cancers

¹ Institut de Cancérologie de Marseille, Département d'Oncologie Moléculaire, Institut Paoli-Calmettes et Unité Mixte de Recherche 599 Institut National de la Santé et de la Recherche Médicale; Départements de ² Oncologie Médicale, ³ Biopathologie, and ⁴ Chirurgie, Institut Paoli-Calmettes; ⁵ Faculté de Médecine, Université de la Méditerranée; ⁶ Ipsogen S.A.; and ⁷ Département d'Anatomopathologie, Hôpital Nord, Marseilles, France

Requests for reprints: Daniel Birnbaum, Unité Mixte de Recherche 599 Institut National de la Santé et de la Recherche Médicale, 27 Bd. Leï Roure, 13009 Marseilles, France. Phone: 33-4-91-75-84-07; Fax: 33-4-91-26-03-64; E-mail: birnbaum{at}marseille.inserm.fr.

Medullary breast cancer (MBC) is a rare but enigmatic pathologic type of breast cancer. Despite features of aggressiveness, MBC is associated with a favorable prognosis. Morphologic diagnosis remains difficult in many cases. Very little is known about the molecular alterations involved in MBC. Notably, it is not clear whether MBC and ductal breast cancer (DBC) represent molecularly distinct entities and what genes/proteins might account for their differences. Using whole-genome oligonucleotide microarrays, we compared gene expression profiles of 22 MBCs and 44 grade III DBCs. We show that MBCs are less heterogeneous than DBCs. Whereas different molecular subtypes (luminal A, luminal B, basal, ERBB2-overexpressing, and normal-like) exist in DBCs, 95% MBCs display a basal profile, similar to that of basal DBCs. Supervised analysis identified gene expression signatures that discriminated MBCs from DBCs. Discriminator genes are associated with various cellular processes related to MBC features, in particular immune reaction and apoptosis. As compared with MBCs, basal DBCs overexpress genes involved in smooth muscle cell differentiation, suggesting that MBCs are a distinct subgroup of basal breast cancer with limited myoepithelial differentiation. Finally, MBCs overexpress a series of genes located on the 12p13 and 6p21 chromosomal regions known to contain pluripotency genes. Our results contribute to a better understanding of MBC and of mammary oncogenesis in general. (Cancer Res 2006; (66)9: 4634-44)

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